The daily dose of Copegus is 800 mg to 1200 mg administered orally in two divided doses. Copegus may interact with abacavir, didanosine, lamivudine, stavudine, tenofovir, zalcitabine, or zidovudine. Tell your doctor all medications you use. Copegus not be used during pregnancy. It is recommended that female patients or female partners of male patients take a pregnancy test before this medication is started, during treatment, and for 6 months after this drug is stopped. If you become pregnant or think you may be pregnant, inform your doctor. It is unknown if this drug passes into breast milk. Because of the potential risk to the infant, breastfeeding while using this medication is not recommended.

Our Copegus (ribavirin) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is Patient Information in Detail?

Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tooth and gum problems may sometimes occur during ribavirin/interferon treatment. Dry mouth can worsen this side effect. Prevent dry mouth by drinking plenty of water or by using a saliva substitute. Brush your teeth well at least twice daily and see your dentist regularly. If you experience vomiting during treatment, rinse out your mouth afterwards to reduce tooth and gum problems.

Seek immediate medical attention if any of these unlikely but very serious side effects occurs: chest pain, jaw/left arm pain, stomach/lower back pain, black/bloody stools.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

SIDE EFFECTS

PEGASYS in combination with COPEGUS causes a broad
variety of serious adverse reactions [see BOXED WARNING and WARNINGS
AND PRECAUTIONS]. The most common serious or life-threatening adverse
reactions induced or aggravated by COPEGUS/PEGASYS include depression, suicide,
relapse of drug abuse/overdose, and bacterial infections each occurring at a
frequency of less than 1%. Hepatic decompensation occurred in 2% (10/574)
CHC/HIV patients [see WARNINGS AND PRECAUTIONS].

Clinical Studies Experience

Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared to rates in the clinical trials of another
drug and may not reflect the rates observed in clinical practice.

Adult Patients

In the pivotal registration trials NV15801 and NV15942,
886 patients received COPEGUS for 48 weeks at doses of 1000/1200 mg based on
body weight. In these trials, one or more serious adverse reactions occurred in
10% of CHC monoinfected subjects and in 19% of CHC/HIV subjects receiving
PEGASYS alone or in combination with COPEGUS. The most common serious adverse
event (3% in CHC and 5% in CHC/HIV) was bacterial infection (e.g., sepsis, osteomyelitis,
endocarditis, pyelonephritis, pneumonia).

The percentage of patients in clinical trials who
experienced one or more adverse events was 98%. The most commonly reported
adverse reactions were psychiatric reactions, including depression, insomnia,
irritability, anxiety, and flu-like symptoms such as fatigue, pyrexia, myalgia,
headache and rigors. Other common reactions were anorexia, nausea and vomiting,
diarrhea, arthralgias, injection site reactions, alopecia, and pruritus. Table
5 shows rates of adverse events occurring in greater than or equal to 5%
subjects receiving pegylated interferon and ribavirin combination therapy in
the CHC Clinical Trial, NV15801.

Overall 39% of patients with CHC or CHC/HIV required
modification of PEGASYS and/or COPEGUS therapy. The most common reason for dose
modification of PEGASYS in CHC and CHC/HIV patients was for laboratory
abnormalities; neutropenia (20% and 27%, respectively) and thrombocytopenia (4%
and 6%, respectively). The most common reason for dose modification of COPEGUS
in CHC and CHC/HIV patients was anemia (22% and 16%, respectively).

PEGASYS dose was reduced in 12% of patients receiving
1000 mg to 1200 mg COPEGUS for 48 weeks and in 7% of patients receiving 800 mg
COPEGUS for 24 weeks. COPEGUS dose was reduced in 21% of patients receiving
1000 mg to 1200 mg COPEGUS for 48 weeks and in 12% of patients receiving 800 mg
COPEGUS for 24 weeks.

Chronic hepatitis C monoinfected patients treated for 24
weeks with PEGASYS and 800 mg COPEGUS were observed to have lower incidence of
serious adverse events (3% vs. 10%), hemoglobin less than 10 g/dL (3% vs. 15%),
dose modification of PEGASYS (30% vs. 36%) and COPEGUS (19% vs. 38%), and of
withdrawal from treatment (5% vs. 15%) compared to patients treated for 48
weeks with PEGASYS and 1000 mg or 1200 mg COPEGUS. On the other hand, the
overall incidence of adverse events appeared to be similar in the two treatment
groups.

* Severe hematologic
abnormalities (lymphocyte less than 500 cells/mm³; hemoglobin less
than 10 g/dL; neutrophil less than 750 cells/mm³; platelet less than
50,000 cells/mm³).

Pediatric Subjects

In a clinical trial with 114
pediatric subjects (5 to 17 years of age) treated with PEGASYS alone or in
combination with COPEGUS, dose modifications were required in approximately
one-third of subjects, most commonly for neutropenia and anemia. In general,
the safety profile observed in pediatric subjects was similar to that seen in
adults. In the pediatric study, the most common adverse events in subjects
treated with combination therapy PEGASYS and COPEGUS for up to 48 weeks were
influenza-like illness (91%), upper respiratory tract infection (60%), headache
(64%), gastrointestinal disorder (56%), skin disorder (47%), and injection-site
reaction (45%). Seven subjects receiving combination PEGASYS and COPEGUS
treatment for 48 weeks discontinued therapy for safety reasons (depression,
psychiatric evaluation abnormal, transient blindness, retinal exudates,
hyperglycemia, type 1 diabetes mellitus, and anemia). Severe adverse events
were reported in 2 subjects in the PEGASYS plus COPEGUS combination therapy
group (hyperglycemia and cholecystectomy).

Growth inhibition was observed
in pediatric subjects. During combination therapy for up to 48 weeks with
PEGASYS and COPEGUS, negative changes in weight for age z-score and height for
age z-score after 48 weeks of therapy compared with baseline were observed [see
WARNINGS AND PRECAUTIONS].

Table 6 : Percentage of Pediatric Subjects with
Adverse Reactions* During First 24 Weeks of Treatment by Treatment Group and
for 24 Weeks Post-treatment (in at Least 10% of Subjects)

System Organ Class

Study NV17424

PEGASYS 180 mcg/1.73 m² x BSA + COPEGUS 15 mg/kg
(N=55)
%

PEGASYS 180 mcg/1.73 m² x BSA + Placebo**
(N=59)
%

General disorders and administration site conditions

Influenza like illness

91

81

Injection site reaction

44

42

Fatigue

25

20

Irritability

24

14

Gastrointestinal disorders

Gastrointestinal disorder

49

44

Nervous system disorders

Headache

51

39

Skin and subcutaneous tissue disorders

Rash

15

10

Pruritus

11

12

Musculoskeletal, connective tissue and bone disorders

Musculoskeletal pain

35

29

Psychiatric disorders

Insomnia

9

12

Metabolism and nutrition disorders

Decreased appetite

11

14

* Displayed adverse drug
reactions include all grades of reported adverse clinical events considered
possibly, probably, or definitely related to study drug.
**Subjects in the PEGASYS plus placebo arm who did not achieve undetectable
viral load at week 24 switched to combination treatment thereafter. Therefore,
only the first 24 weeks are presented for the comparison of combination therapy
with monotherapy.

In pediatric subjects
randomized to combination therapy, the incidence of most adverse reactions were
similar for the entire treatment period (up to 48 weeks plus 24 weeks
follow-up) in comparison to the first 24 weeks, and increased only slightly for
headache, gastrointestinal disorder, irritability and rash. The majority of
adverse reactions occurred in the first 24 weeks of treatment.

Laboratory Test Abnormalities

Adult Patients

Anemia due to hemolysis is the
most significant toxicity of ribavirin therapy. Anemia (hemoglobin less than 10
g/dL) was observed in 13% of all COPEGUS and PEGASYS combination-treated
patients in clinical trials. The maximum drop in hemoglobin occurred during the
first 8 weeks of initiation of ribavirin therapy [see DOSAGE AND
ADMINISTRATION].

Table 7 : Selected Laboratory Abnormalities During
Treatment With COPEGUS in Combination With Either PEGASYS or Intron A

Laboratory Parameter

PEGASYS + Ribavirin 1000/1200 mg 48 wks
(N=887)

Intron A + Ribavirin 1000/1200 mg 48 wks
(N=443)

Neutrophils (cells/mm³)

1,000 < 1,500

34%

38%

500 < 1,000

49%

21%

< 500

5%

1%

Platelets (cells/mm³)

50,000 - < 75,000

11%

4%

20,000 - < 50,000

5%

< 1%

< 20,000

0

0

Hemoglobin (g/dL)

8.5 -9.9

11%

11%

< 8.5

2%

< 1%

Pediatric Patients

Decreases in hemoglobin,
neutrophils and platelets may require dose reduction or permanent
discontinuation from treatment [see DOSAGE AND ADMINISTRATION]. Most
laboratory abnormalities noted during the clinical trial returned to baseline
levels shortly after discontinuation of treatment.

Table 8 : Selected
Hematologic Abnormalities During First 24 Weeks of Treatment by Treatment Group
in Previously Untreated Pediatric Subjects

Laboratory Parameter

PEGASYS 180 mcg/1.73 m² x BSA + COPEGUS 15 mg/kg
(N=55)

PEGASYS 180 mcg/1.73 m² x BSA + Placebo*
(N=59)

Neutrophils (cells/mm³)

1,000 - < 1,500

31%

39%

750 - < 1,000

27%

17%

500 - < 750

25%

15%

< 500

7%

5%

Platelets (cells/mm³)

75,000 - < 100,000

4%

2%

50,000 - < 75,000

0%

2%

< 50,000

0%

0%

Hemoglobin (g/dL)

8.5 - < 10

7%

3%

< 8.5

0%

0%

* Subjects in the PEGASYS plus
placebo arm who did not achieve undetectable viral load at week 24 switched to
combination treatment thereafter. Therefore, only the first 24 weeks are
presented for the comparison of combination therapy with monotherapy.

In patients randomized to
combination therapy, the incidence of abnormalities during the entire treatment
phase (up to 48 weeks plus 24 weeks follow-up) in comparison to the first 24
weeks increased slightly for neutrophils between 500 and 1,000 cells/mm³ and
hemoglobin values between 8.5 and 10 g/dL. The majority of hematologic
abnormalities occurred in the first 24 weeks of treatment.

Postmarketing Experience

The following adverse reactions
have been identified and reported during post-approval use of PEGASYS/COPEGUS
combination therapy. Because these reactions are reported voluntarily from a
population of uncertain size, it is not always possible to reliably estimate
their frequency or establish a causal relationship to drug exposure.